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Biomedical subjects

A M Ward

Publications and source records attributed to A M Ward.

At least 37 records · Page 2Linked to original sources
PubMed1998

Ureteropelvic junction obstruction in children. Unique considerations for open operative intervention.

The treatment of UPJ obstruction in children should be approached in a fashion that recognizes the differences between children and adults. Radiographic definition of the urinary tract is different in children than in adults because of the size of the child and technical difficulties with instrumentation. Retrograde pyelography, in general, is not necessary in children, although this decision must be individualized. The surgical incision should be chosen based on the size of the child and the unique considerations of individual renal anatomy and pathology, as well as the surgeon's experience. In children, tubeless surgery may be performed with excellent results, however, diversion with nephrostomies and stents may be necessary in selected cases. With attention to technical details and the unique considerations in children, the results of repair of the UPJ should be excellent and reproducible.

Child↗
PubMed1998

Immunogenicity and efficacy of DNA vaccines encoding influenza A proteins in aged mice.

Influenza is a leading cause of morbidity and mortality in older persons. The current influenza vaccine is only modestly successful, in part because of an age-related decline in immunogenicity and also because it induces only type-specified immunity. To overcome this, we evaluated DNA vaccines encoding A/PR8/34 haemagglutinin (HA) and nucleoprotein (NP) in young and aged BALB/c mice. Control mice were given formalin-inactivated A/PR8/34, control DNA, or a non-lethal dose of PR8. Aged mice given HA DNA developed slightly lower anti-HA serum antibodies than young mice; however, both young and aged mice were protected from a homotypic PR8 challenge. Following vaccination with NP DNA, both young and aged mice developed anti-NP bulk cytotoxic T-lymphocyte (CTL) activity and pCTL frequency similar to control animals. When challenged with a low dose of A/HK/68 (H3N2) influenza virus, both young mice and aged mice showed significant protection as measured by inhibition of weight loss. When challenged with a relatively high dose of A/HR/68 (H3N2) influenza virus, however, the anti-NP vaccine only partially protected young mice and failed to protect aged mice. These data demonstrate that DNA-based vaccines are immunogenic in aged animals, but suggest that factors other than the age-related decline in CTL activity also contribute to the increased morbidity and mortality of influenza in the elderly.

Aging↗
PubMed1998

The value of prostate specific antigen (PSA) density and free: total PSA ratio in selecting patients with a normal digital rectal examination and intermediate total PSA levels for further investigation.

OBJECTIVES: To examine the use of prostate-specific antigen (PSA) density (PSAD) and free to total PSA ratio (f/tPSA) in enhancing the specificity of PSA in the diagnosis of prostate cancer in patients with a total PSA (tPSA) of 4-10 ng/mL and with a normal digital rectal examination (DRE). PATIENTS AND METHODS: The study comprised 77 consecutive men in whom the fPSA and tPSA levels were obtained before DRE and transrectal ultrasonography-guided sextant prostate biopsy. Prostate cancer was found in 39 patients and the histology was benign in 38. Receiver operator characteristic curves, obtained from all 77 patients, were used to determine the optimal thresholds for PSAD and f/tPSA in detecting cancer. A subset of 28 patients, including seven with prostate cancer, was identified who had a normal DRE and a tPSA of 4-10 ng/mL; PSAD and f/tPSA values were applied at the optimal thresholds to assess their use in identifying those patients with cancer. RESULTS: When applied to the selected group of 28 patients, the PSAD (threshold 0.15) failed to identify any with prostate cancer. The f/tPSA (threshold 0.12) yielded a sensitivity of 65% and a specificity of 38%, identifying only three of seven patients with cancer. By increasing the threshold to 0.25, six patients were correctly identified, giving a sensitivity of 86%, with a lower specificity of 14%. CONCLUSIONS: These findings suggest that the neither PSAD nor f/tPSA either significantly reduce the negative biopsy rate or identify patients at greater risk of prostate cancer, particularly when the tPSA is equivocal at 4-10 ng/mL.

Aged↗
PubMed1998

Are autoimmune thyroid dysfunction and depression related?

The objective of this study was to examine the relationship between autoimmune thyroid disease and depression in perimenopausal women. Thyroid function [TSH, free T4, and thyroid peroxidase antibodies (TPO-Ab)] and depression (using the Edinburgh Depression Scale) were assessed cross-sectionally together with other determinants of depression. The subjects were 583 randomly selected perimenopausal women (aged 47-54 yr) from a community cohort of 6846 women. The main outcome measures were the occurrence of thyroid dysfunction (abnormal free T4 and/or TSH or elevated levels of TPO-Ab) and the concomitant presence of depression according to the Edinburgh Depression Scale. Neither biochemical thyroid dysfunction nor menopausal status was related to depression. Apart from several psycho-social determinants (the occurrence of a major life event, a previous episode of depression, or financial problems), an elevated level of TPO-Ab (> or = 100 U/mL) was significantly associated with depression (odds ratio, 3.0, 95% confidence interval, 1.3-6.8). We conclude that women with elevated TPO-Ab levels are especially vulnerable to depression, whereas postmenopausal status does not increase the risk of depression.

Autoantibodies↗
PubMed1997

Questioning behaviour in general practice: a pragmatic study.

OBJECTIVE: To study the extent to which general practitioners' questioning behaviour in routine practice is likely to encourage the adoption of evidence based medicine. DESIGN: Self recording of questions by doctors during consultations immediately followed by semistructured interview. SETTING: Urban Australian general practice. SUBJECTS: Random sample of 27 general practitioners followed over a half day of consultations. MAIN OUTCOME MEASURES: Rate of recording of clinical questions about patients' care which doctors would like answered; frequency with which doctors found answers to their questions. RESULTS: Doctors asked a total of 85 clinical questions, at a rate of 2.4 for every 10 patients seen. They found satisfactory answers to 67 (79%) of these questions. Doctors who worked in small practices (of one or two doctors) had a significantly lower rate of questioning than did those in larger practices (1.6 questions per 10 patients v 3.0 patients, P = 0.049). No other factors were significantly related to rate of questioning. CONCLUSIONS: These results do not support the view that doctors routinely generate a large number of unanswered clinical questions. It may be necessary to promote questioning behaviour in routine practice if evidence based medicine and other forms of self directed learning are to be successfully introduced.

Decision Making↗
PubMed1997

Serum IgD levels in children under investigation for and with defined immunodeficiency.

BACKGROUND: The function and regulation of circulating IgD are unclear. Serum IgD levels were increased in a wide range of immunological diseases but these associations did not give a clue to the regulation of serum IgD production. METHODS: Serum IgD levels in 131 children with various non-HIV-related immunodeficiency diseases were investigated to examine their relationship with immunoglobulin or antibody production and activation of the immune system. Data from a group of 109 nonimmunodeficient children were also available for comparison. RESULTS: There was a bimodal distribution of serum IgD levels. In 87 patients IgD levels fell below the limit of detection of 5 IU/ml, while the remainder showed an approximately normal distribution skewed to the right after log transformation. The proportion of children with undetectable IgD levels (< 5 IU/ml) was significantly increased in immunodeficient children (87/131 vs. 28/109, p < 0.001). No difference in the occurrence of immunoglobulin or antibody deficiencies was demonstrated in immunodeficient children with detectable and nondetectable IgD levels. There was a positive correlation of serum IgD with age, serum IgA and IgE, white blood count and CD4+CD25+ lymphocytes but not with other immunoglobulin isotypes or immune activation markers. CONCLUSION: Determination of serum IgD levels did not seem to be of particular clinical benefit in the investigation of HIV-negative immunodeficient children and serum IgD levels were not associated with the general picture of immune activation. Observed distribution patterns and associations may have implications for the regulation of serum IgD production.

Age Factors↗
PubMed1995

Comparison of monoclonal antibodies for flow cytometric analysis of HLA-B27 antigen.

HLA-B27 is an antigen associated with the disease ankylosing spondylitis. Ninety percent of Caucasians with ankylosing spondylitis possess the HLA-B27 antigen. However, only 20% of Caucasians with the HLA-B27 antigen will develop the disease. Defining the presence or absence of the HLA-B27 antigen can be helpful in differentiating ankylosing spondylitis from juvenile rheumatoid arthritis. In this study, we evaluated the application of two monoclonal antibodies (MoAbs), using flow cytometric analysis for the detection of HLA-B27 antigen. After an initial comparison of HLA-B27 analysis by flow cytometry to the standard microlymphocytotoxicity assay, cutoffs were established to differentiate HLA-B27 positive from HLA-B27 negative. One MoAb showed very reliable results with > 99% accuracy in discriminating HLA-B27 positive from HLA-B27 negative samples. Various parameters were investigated to obtain the optimum results and showed that incubation time, reagent lot, and the flow cytometric instrument can affect the results. We concluded that a reliable MoAb and flow cytometry are valuable for the rapid and inexpensive determination of HLA-B27 typing in the clinical setting. However, testing conditions can affect the accuracy of results; therefore, adequate parallel testing in various conditions must be performed in order to establish the proper standards.

Antibodies, Monoclonal↗
PubMed1995

Attendance patterns in general practice.

OBJECTIVE: To determine the completeness of data acquired previously on the attendance patterns of patients visiting three general practices and the exclusivity of attendance at these practices. DESIGN: A retrospective comparison of attendance data with data extracted from the Health Insurance Commission database. Three study practices were investigated to give a rough cross-section of general practice in Western Australia. RESULTS: Eighty-nine per cent of patients and 92% of services recorded in our earlier study were also recorded by the HIC, with 31% of patients also attending another general practice during the six months, mostly only once or twice. However, there was considerable variation between practices in data match and attendance at other practices. CONCLUSIONS: We found a high level of completeness of data. Sixty-nine per cent of patients attended no other practice during the six months, indicating that doctors in the study practices have some opportunity to provide continuity of care to their patients. The implications for patients' needs and doctors' resources of variations in attendance patterns need to be examined further.

Adolescent↗
PubMed1995

Alpha-1-antitrypsin phenotypes and associated disease patterns in neurological patients.

INTRODUCTION: Alpha-1-antitrypsin (AAT) deficiency is usually associated with lung or liver disease. It is often detected as a qualitative reduction of the alpha-1 band on the serum protein electrophoretic pattern. MATERIAL AND METHODS: We examined the protein electrophoretic pattern in sera of 22980 unselected consecutive patients with neurological disorders and noted a reduced alpha-1 band in 88. Their phenotypes were compared with the clinical disease. RESULTS: 75 patients had a deficient or non-M and 13 the usual MM phenotype. Contrary to in the general population, PiMZ was four times more common than PiMS. Vascular disease was more common in patients with PiMZ while multiple sclerosis significantly more frequent in patients with PiMS than with other phenotypes, including PiMM. CONCLUSIONS: Other genetic abnormalities have previously been found in AAT associated with multiple sclerosis, but not PiMS. Since PIMS leads to modest reduction of AAT activity, the association may be through other mechanisms than reduced protease activity.

Adult↗
PubMed1994

Management of type 2 diabetes in Western Australian metropolitan general practice.

The purpose of this study was: (1) to record GP opinions, practices and outcomes for the care of Type 2 Diabetes Mellitus (DM2), (2) compare practice facilities and process of care with a criterion of recommended competent care and (3) determine if there were any differences between vocationally registered and non-vocationally registered GPs. A random sample of 204 metropolitan doctors from 124 practices was selected and an audit performed on 467 of their patient records. GPs pursued good blood sugar control and advocated lifestyle changes before hypoglycaemic drugs. Over 80% regard uncomplicated DM2 as a condition for general practice management. However, only 15% conducted an annual diabetes check, 9% had a diabetic register, 6% a diabetic recall system and 8% used a diabetic health care checklist for monitoring their patients. The most commonly recorded processes of medical audit in the previous 12 months were: blood pressure (94%), duration of diabetes (72%), blood glucose (70%), diet (66%), body weight (56%), HBA1c (52%) and ophthalmoscopy (50%). The least commonly recorded processes of care were body mass index (5%), inspection of the feet (18%), enquiries about vaginitis or impotence (23%). The amount of exercise, alcohol and tobacco was recorded in only 34% of records. Hypoglycaemic drugs were used appropriately but the most commonly used drugs for treating hypertension in DM2 patients were thiazide diuretics and beta-blockers. Vocationally registered (VR) doctors had better records, higher process of care scores and more were willing to participate in the study than non-vocationally registered (NVR) doctors. However, there was no difference in metabolic control between patients from either group. The use of a Diabetic Health Care Checklist would improve diabetes care especially in the search for early complications and in the recording of HBA1c and other metabolic parameters. The drugs commonly used to control hypertension can have adverse effects on glucose and lipid metabolism and should be replaced with glucose and lipid neutral drugs.

Adult↗
PubMed1994

Stability of attendance in general practice.

Data on the attendances of all patients at three general practices in Western Australia for two 6-month periods 11 months apart were collected as part of a previous study. The present study examined the stability of the attendance patterns of the patients over the two study periods in terms of number of patients, number of visits and diagnoses. The patients who attended in both study periods were classified into four attendance groups: low to low; low to high; high to low; and high to high. The age, sex and diagnoses for each were compared. The results showed that whilst the patient populations remained constant over the two periods, these populations were not comprised of the same patients. Only 45% of those who attended in the first 6 months also attended in the second. Similarly, whilst 8% of patients in each study period were classified as high attenders, only 22% of the high attenders in the first period were also high attenders in the second. The long-term high attenders were older and suffered from chronic diagnoses. The short-term high attenders were found to suffer from more self-limiting diseases and conditions such as depression and pregnancy.

Adolescent↗
PubMed1994

The significance of elevated basal follicle stimulating hormone in regularly menstruating infertile women.

Elevated plasma follicle stimulating hormone (FSH) during the reproductive life is an early manifestation of ovarian ageing. The presence of elevated basal FSH in young, regularly menstruating women may represent a stage of menopausal transition consequent on premature ovarian failure. A total of 48 regularly menstruating, infertile women aged < 40 years, with high FSH and aged-matched controls with normal FSH underwent detailed monitoring of endocrine and follicle growth during one complete menstrual cycle. During the same cycle, detailed immunological screening was performed and the epidemiological features of all subjects were also reviewed. Subjects in the high FSH group had significantly higher basal FSH, luteinizing hormone (LH) and follicular phase LH concentrations. Despite their normal preovulatory oestradiol production, the high FSH group showed significantly slower follicular growth, smaller follicle diameter and lower luteal phase salivary progesterone. All these features have been described in older women during their menopausal transition. In addition, the prevalence of autoimmune antibodies was significantly higher in the high FSH group. This study suggests that infertile women with elevated FSH are in their perimenopause despite having regular ovulatory and apparently normal cycles. An autoimmune basis is suggested as a factor underlying their premature ovarian failure. Further endocrinological and autoimmunological follow-up is recommended.

Adult↗
PubMed1994

New international reference preparation for proteins in human serum (RPPHS).

Quality-control surveys in recent years, in various parts of the world, have shown poor between-laboratory agreement for measurements of plasma proteins. Despite the existence of international reference materials distributed by the World Health Organization, standards produced by diagnostics manufacturers and professional organizations differ significantly in their ascribed values. The reasons for this are complex but include poor availability of the primary materials, confusion about their use, and the fact that their turbidity on reconstitution precludes their use in modern optical immunoassays. This unfortunate situation led to an important initiative to produce sufficient quantities of a widely available, optically clear secondary reference material for plasma proteins that could be used worldwide by manufacturers, professional organizations, and laboratories. Here we present an overview on how the laboratory community, including manufacturers, clinical laboratories, professional societies, and regulators, has reached what we consider is a successful conclusion to a difficult problem.

Blood Proteins↗
PubMed1992

Beta-naphthoflavone induction of a cytochrome P-450 arachidonic acid epoxygenase in chick embryo liver distinct from the aryl hydrocarbon hydroxylase and from phenobarbital-induced arachidonate epoxygenase.

Cytochrome P-450-mediated arachidonic acid metabolism in chick embryo liver microsomes was increased by both Ah receptor-dependent (2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and beta-naphthoflavone) and independent (phenobarbital) P-450 inducers. Arachidonic acid epoxides and monohydroxyeicosatetraenoic acids were increased 9-12-fold. omega-1-OH arachidonic acid was also significantly increased by TCDD and beta-naphthoflavone while omega-OH arachidonic acid, the main metabolite in uninduced livers, was decreased by all three agents. The P-450s catalyzing the enhanced arachidonate metabolism in beta-naphthoflavone- and phenobarbital-treated liver were investigated in reconstituted systems containing wholly or partially purified P-450s. beta-Naphthoflavone induced formation of a 55-kDa P-450 selective for arachidonate metabolism and for epoxygenation in particular. This P-450 was purified (beta NFAA). It was found to be distinct from a 54.5-kDa beta-naphthoflavone-induced P-450 catalyzing aryl hydrocarbon hydroxylase and 7-ethoxyresorufin deethylase (designated NF1). Mean turnover numbers for arachidonate epoxygenase, aryl hydrocarbon hydroxylase, and 7-ethoxyresorufin deethylase were 11.2, 0.56, and 0.04, respectively, for reconstituted beta NFAA and 0.33, 11.8, and 2.4 for NF1. beta NFAA and NF1 also differed in chromatography elution characteristics and N-terminal amino acid sequences. Both were low spin, with carbon monoxide binding peaks at 448 nm. The phenobarbital-induced arachidonate epoxygenation was catalyzed by P-450 fractions containing the main 48- and 49-kDa phenobarbital-induced P-450s; fractions in which the 49-kDa P-450 predominated were the most active. Turnover numbers for arachidonic acid epoxygenation were not correlated with those for aminopyrine demethylation or 7-ethoxycoumarin deethylation for P-450s from phenobarbital-treated livers or with aryl hydrocarbon hydroxylase, 7-ethoxyresorufin deethylase, or 7-ethoxycoumarin deethylase for P-450s from beta-naphthoflavone-treated livers. Also, different P-450s catalyzed the epoxygenation and the omega-hydroxylation of arachidonic acid in both beta-naphthoflavone- and phenobarbital-treated livers. The findings support a physiologic role for P-450-induced arachidonate metabolism and provide a basis for a possible link between TCDD's induction of P-450 and alterations of cellular homeostasis.

Amino Acid Sequence↗
PubMed1992

Free beta human choriogonadotropin in Down's syndrome screening: a multicentre study of its role compared with other biochemical markers.

To ascertain the value of maternal serum free beta-human choriogonadotropin subunit measurement in Down's syndrome screening and to compare its effectiveness when screening with a variety of biochemical markers, we have evaluated maternal serum free beta-human choriogonadotropin, total human choriogonadotropin, alpha-fetoprotein and unconjugated oestriol in a large multicentre study of over 2800 unaffected cases and 90 affected cases, the largest collection of Down's cases ever reported. Of all the markers identified to date, free beta-human choriogonadotropin is the marker of choice for use in Down's syndrome screening. When used in early gestation (14-16 weeks) in combination with alpha-fetoprotein and maternal age, it will allow the detection of 77% of Down's cases. A side-by-side comparison with the performance of total human choriogonadotropin shows the superior detection efficiency of free beta-human choriogonadotropin. Unconjugated oestriol adds nothing further to the detection rate compared with the use of alpha-fetoprotein and free beta-human choriogonadotropin alone, and its use results in a 1% increase in false positive rate. We conclude that unconjugated oestriol has no value in Down's screening. The superior detection rate obtained using free beta-human choriogonadotropin is a result of superior detection of Down's cases in women under 30 years old, where the free beta-human choriogonadotropin combination detects 100% more cases than does the total human choriogonadotropin combination.

Biomarkers↗